It is not about the bike, it is about the pedaling: forced exercise and Parkinson's disease

Abstract

Forced exercise has resulted in neuroprotective effects and improved motor function in animal studies. These promising results have not yet been translated fully to humans with Parkinson's disease (PD), as traditional exercise interventions have not yielded global improvements in function. A novel forced exercise intervention is described that has resulted in improved motor function and central nervous system function in PD patients.

Figure 1.

Schematic depicting the proposed effect of forced exercise (FE) on central nervous center (CNS) structure and function. Diminished neural activity in the Parkinson’s disease (PD) brain is depicted on the left portion of the illustration. It is proposed that FE results in an increase in the quantity (high rate of pedaling) and quality (consistent pedaling pattern) of intrinsic feedback from the Golgi tendon organs (GTO) and muscle spindles. This increased afferent information may trigger the release of neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; IGF₃, insulin growth factor) and possibly the neurotransmitter dopamine. The elevation of neurotrophic factors and dopamine has the potential to impact CNS structure and function. Proposed structures and function (matched by colors) that may be impacted by an elevation neurotrophic factors and dopamine are shown in the middle of the illustration. For PD, patients’ FE leads to improvements in motor control and an increase in the cortical activation. These changes in the CNS in PD positively affect the symptoms of this neurodegenerative disease and may serve as a model for the treatment of other neurological conditions. VTA, ventral tegmental area; ANS, autonomic nervous system. (Copyright © 2011 Cleveland Clinic Center for Medical Art & Photography. If you would like to reuse this image, please seek permissions directly from Cleveland Clinic Center for Medical Art & Photography. Used with permission.)

Figure 2.

A. Tandem cycle used to deliver forced exercise (FE). B. Total power measured at the rear wheel (solid line) and power produced by the captain (dash line) and stoker (dotted line) for a 25-min test session. The stoker was passive for the first 5 min of the session.

Figure 3.

Blinded clinical ratings Unified Parkinson’s Disease Rating Scale, Part III Motor Section (UPDRS-III) scores for patients in the voluntary exercise (VE; open bars) and forced exercise (FE; filled bars) groups at baseline, midpoint (4 wk of exercise), end of treatment (EOT). EOT + 2 wk exercise cessation and EOT + 4 wk exercise cessation.

Figure 4.

A. System used to objectively quantify bimanual upper extremity function. The goal of the task is to disconnect the two force transducers from one another. The upper transducer is held by the manipulating hand, whereas the lower transducer is grasped by the stabilizing limb. B. Representative grip-load coordination plots for the stabilizing (solid lines) and manipulating (dotted lines) limbs for a patient in the voluntary exercise (VE) (left) and forced exercise (FE) (right) groups at baseline and at end of training (EOT). Grip-load relationships in Parkinson’s disease (PD) typically are uncoupled and irregular. After 8 wk of FE, grip-load relationships seem more coupled but unchanged after VE. C. Mean changes in grip time delay (grip onset manipulating–grip onset stabilizing). Delays were reduced significantly in the FE group from baseline to EOT and EOT + 4. Standard deviations also were reduced after the intervention. No changes in grip time delay were noted in the VE group. D. Mean changes in rate of force production in the manipulating hand at baseline, EOT, and EOT + 4. Rates of force production were increased significantly after 8 wk of FE but were reduced slightly after VE. Error bars = standard deviations. (Reprinted from (22). Copyright © 2009 Society for Neuroscience. Used with permission.)

Figure 5.

Center of pressure for all dexterity trials for patients in the forced exercise (FE) (x) and voluntary exercise (VE) (o) groups at baseline, end of training (EOT), and EOT + 4 wk. The upper limb performs the manipulating action, whereas the lower limb acts to stabilize the device. Ellipses define the area of spread to encompass 95% of the data. Forced exercise resulted in significantly less spread in center of pressure (COP) than VE. Smaller ellipses indicate less variability in COP and digit placement. (Reprinted from (22). Copyright © 2009 Society for Neuroscience. Used with permission.)

Figure 6.

Cortical and subcortical activation maps across subjects. Highlighted areas indicate areas in the brain where increased blood flow, or cortical activation is present with hand movement tasks during scanning. This figure is an average of nine patients with Parkinson’s disease (PD) under three conditions: on antiparkinsonian medication, off antiparkinsonian medication, and 3-h post forced exercise (FE) while off antiparkinsonian medication. The pattern of cortical and subcortical activation was similar while patients were on medication and following FE while off medications.